Share your insights

Help us by sharing what content you've recieved in your exams


Interpretation of urea and electrolytes

Please note OSCEstop content is for educational purposes only and not intended to inform clinical practice. OSCEstop and authors take no responsibility for errors or the use of any information displayed. Drugs and doses are intended for non-pregnant adults, who are not breastfeeding, with normal renal and hepatic function.

Urea and creatinine

Physiology

Creatinine
  • Creatine is a substance produced primarily by the liver 
  • Creatine is phosphorylated to creatine phosphate, which is used as an energy store for muscles
  • To produce energy, creatine phosphate is broken down to creatine and phosphate, which allows ADP to be converted to ATP 
  • Creatine is metabolised to the waste product creatinine, which passes to the kidneys where it is excreted
  • Changes in creatinine concentration are fairly specific for determining kidney injury, but baseline level depends on muscle mass
Urea
  • Ammonia is a toxic waste product produced during amino acid catabolism
  • Ammonia is converted to urea in the liver by the ‘urea cycle’
  • Urea then passes to the kidneys where it is excreted
  • Serum urea concentration also rises in kidney injury but it is not specific for this. Other causes of high/low urea include:
    • ↑urea = dehydration, GI bleeding, increased protein breakdown (trauma, infection, malignancy), high protein intake
    • ↓urea = malnutrition, liver disease, pregnancy

Acute kidney injury

Acute kidney injury (AKI) = rise in serum creatinine >50% from baseline, or urine output <0.5ml/kg/hour for 6 hours.

Determine if AKI is pre-renal, renal, or post-renal.

ALL patients need:

  • Urine dipstick (interpreted in context of history)
  • Bloods: FBC ± haematinics, U&Es, CRP, Ca2+, PO43-, PTH
  • VBG: check for: metabolic acidosis/low bicarbonate (may need weak bicarbonate infusion); and hyperkalaemia
  • Accurate fluid balance chart (requires catheterisation)
  • Stop nephrotoxic drugs and stop/dose-reduce renal excreted drugs

Pre-renal AKI (70%) – caused by renal hypoperfusion

  • Causes: hypovolaemia/sepsis (most common AKI cause), renovascular disease, cardiorenal failure (increased venous pressure reduces renal perfusion pressure)
  • Suggested by: history, dehydration, hypotension, rise in urea greater than rise in creatinine
  • Investigation:

  • Treatment: treat cause (IV fluids in hypovolaemia)
  • Complications: acute tubular necrosis

Intrinsic AKI (20%) – caused by renal damage

  • Causes
    • Acute tubular necrosis (ischaemic or nephrotoxic): suggested by renal hypoperfusion or tubular nephrotoxin
    • Acute interstitial nephritis: suggested by causative drugs, sometimes with eosinophillia or rash
    • Glomerulonephritis: suggested by haematuria/proteinuria on dip and other glomerulonephritis/vasculitic symptoms
    • Thrombotic microangiopathy (e.g. microangiopathic haemolytic anaemia, hypertensive emergency, scleroderma renal crisis): suggested by anaemia, thrombocytopaenia ± haemolysis evidence (e.g. hyperbilirubinaemia, fragments on film)
  • Investigation:
    • Urine dipstick: blood +++ protein +++ in glomerulonephritis; in acute tubular necrosis, urine is usually bland
    • Urine protein:creatinine ratio (to quantify and monitor proteinuria if dipstick is positive for protein; <15mg/mmol = normal; >300mg/mmol = nephrotic)
    • NB: urine protein:creatinine ratio (mg/mmol) X 10 ≈ 24 hour protein loss (mg)
  • Possible further tests
    • Nephritic screen (if suspect glomerulonephritis): antinuclear antibodies, anti-neutrophil cytoplasmic antibodies, anti-glomerular basement membrane antibody, complement, rheumatoid factor, anti-streptolysin O titre, anti-DNase B, hepatitis B/C serology, HIV serology, antiphospholipid antibodies
    • Myeloma screen: immunoglobulins/protein electrophoresis and serum free light chains
      If thrombocytopenia/suspicion of haemolysis: blood film, lactate dehydrogenase, haptoglobin, bilirubin
    • Creatinine kinase (if rhabdomyolysis suspected)
    • Renal biopsy indications: unexplained AKI, suspected glomerulonephritis, positive nephritic screen, persistent acute tubular necrosis, or suspected interstitial nephritis
      • Urgent renal biopsy if rapidly progressive glomerulonephritis suspected (suggested by rapid loss of kidney function, worsening severe proteinuria/haematuria, and nephritic syndrome)
  • Treat cause, for example:
    • Stop causative agent for acute interstitial nephritis
    • Corticosteroids, diuretics and ACE inhibitor may be required for glomerulonephritis

Post-renal AKI (10%) – caused by obstruction of the urinary tract

  • Cause: urinary tract obstruction
    • Ureters: ureteric calculi, vesico-ureteric reflux, ureteric stricture, tumour (e.g. transitional cell carcinoma), extrinsic compression
    • Bladder: neurogenic bladder, bladder calculi, tumour (e.g. bladder carcinoma)
    • Urethra: benign prostatic hypertrophy, prostate cancer, stricture, blocked catheter
  • Suggested by: history, urea and creatinine raised in equal proportion
  • Investigation:
    • Bladder scan
    • Renal tract USS
  • Treatment: relieve obstruction (catheter if urethral; nephrostomy/ureteric stent if ureteric) and treat cause
  • Complications: hydronephrosis (can progress to irreversible renal damage)

Indications for renal replacement therapy in acute kidney injury

 

Refractory…

  • Acidosis – pH<7.2
  • Electrolyte abnormalities (hyperkalaemia, hyponatraemia, hypercalcaemia) – K+>6.5 or ECG changes
  • Intoxicants (methanol, lithium, salicylates)
  • Overload – acute pulmonary oedema
  • Uraemia – urea >60, uraemic pericarditis or encephalopathy

 

NB: in chronic kidney disease, regular dialysis is required when the GFR is <15ml/minute, and there are symptoms or complications of kidney disease.

Chronic kidney disease

Chronic kidney disease = presence of marker of kidney damage (e.g. albuminuria) or decreased GFR for >3 months

Commonest causes
  1. Diabetes (secondary glomerular disease)
  2. Chronic hypertension
  3. Chronic glomerulonephritis
  4. Polycystic kidney disease
Determining cause
  • History
  • Urine dipstick
  • Renal USS
  • Renal biopsy if required
Management
  • Delay progression: manage cause; plus consider ACE-inhibitor, SGLT-2-inhibitor, and non-steroidal mineralocorticoid receptor antagonist where indicated
  • Reduce cardiovascular risk: lifestyle advice; blood pressure control; statin; aspirin (if cardiovascular disease)
  • Treat complications:
    • Oedema → low salt diet, fluid restriction ± furosemide
    • Anaemia → iron supplementation ± erythropoietin
    • Secondary hyperparathyroidism →
      • Active vitamin D therapy,e.g. alfacalcidol, calcitriol
      • Dietary phosphate restriction ± phosphate binders, e.g. calcium edetate/sevelamer
      • PTH-control with parathyroidectomy or cinacalcet
    • Acidosis → sodium bicarbonate
    • Hyperkalaemia → dietary potassium restriction
    • Acidosis → sodium bicarbonate
  • Dialysis/transplant consideration (when GFR is <15ml/minute, and there are symptoms or complications of kidney disease)

Sodium

Physiology

  • Na+ is an extracellular ion
  • H2O follows solutes due to osmosis (e.g. Na+, albumin)
  • Aldosterone increases Na+ reabsorption (in exchange for K+) from the distal convoluted tubule
  • Antidiuretic hormone causes reabsorption of H2O (alone) from the collecting duct

Hyponatraemia

→ nausea/vomiting, headache, confusion, seizures, reduced consciousness

Causes
Hyponatraemia causes
Investigations
  • Plasma osmolality (to confirm if true hyponatraemia) + glucose
    • Low = true hyponatraemia 
    • Normal = false hyponatraemia (‘pseudohyponatraemia’ due to hyperlipidaemia or hyperproteinemia)
    • High = dilutional (due to hyperglycaemia, e.g. in hyperosmolar hyperglycaemic state/DKA; alcohols; or mannitol)
  • Urinary sodium and osmolality (to determine whether the problem is occurring in the kidneys or elsewhere)
  • Specific tests to investigate for specific causes, for example:
    • SIADH: low plasma osmolality (<275) with high urine osmolality (>100) and high urine sodium (>30); investigate cause
    • Adrenal insufficiency: 9am cortisol screening test, Synacthen (synthetic ACTH) test 
    • Hypothyroidism: TFTs

Check TFTs and 9am cortisol in all euvolaemic patients 

Management
  • Treat cause
  • Sodium correction
    • Severe symptoms (e.g. vomiting, seizures, low GCS), regardless of cause: consider 3% hypertonic saline (e.g. 150ml over 20 minutes, repeated if necessary), usually in ICU with close monitoring 
    • Hypovolaemic: replace lost fluid with 0.9% saline/Hartmann’s solution – slowly if chronic, e.g. 1L over 12 hours
    • Euvolaemic: treat cause 
    • If SIADH or oedematous: fluid restrict to 1 litre/day (excess H2O causes dilutional hyponatraemia); consider demeclocycline (± tolvaptan) for fluid restriction-resistant SIADH; diuretics for heart failure

NB: chronic hyponatraemia (onset over 48 hours) must be corrected slowly, i.e. maximum 10mmol/L change in 24 hours (risk of osmotic change causing osmotic demyelination syndrome).

Hypernatraemia 

→ thirst, confusion, muscle twitching/spasms

Causes
  • Euvolaemic = iatrogenic (e.g. excess IV sodium-containing fluids, sodium-containing drugs)
  • Hypovolaemic
    • Producing small volumes of concentrated urine (normal response to hypovolaemia) = dehydration
    • Not producing small volumes of concentrated urine (abnormal response to hypovolaemia)
      • Diabetes insipidus = urine osmolality <750 + serum osmolality >300 (kidneys not reabsorbing sufficient H2O)
      • Osmotic diuresis, e.g. due to hyperglycaemia or osmotic diuretics (kidneys losing H20 and solutes)
Investigation
  • Urine and serum osmolality 
  • Fluid deprivation test to confirm diabetes insipidus
Management
  • Treat cause
  • Sodium correction
    • Hypovolaemic (signs include hypotension, tachycardia, orthostatic hypotension): replace deficit with 0.9% saline/Hartmann’s solution
    • Euvolaemic: 5% dextrose – slowly if chronic, e.g. 1L over 12 hours

NB: chronic hypernatraemia (onset over 48 hours) must be corrected slowly, i.e. maximum 10mmol/L change in 24 hours (risk of osmotic change causing osmotic demyelination syndrome).

Potassium

Physiology

  • K+ is 90% intracellular
  • Multiple pumps affect serum K+:

Hypokalaemia 

→ arrhythmias, tremor, muscle weakness/cramps, constipation 

Causes
  • Increased renal loss
    • Diuretics (except potassium-sparing diuretics) 
    • Endocrinological (steroids, Cushing’s syndrome, hyperaldosteronism)
    • Renal tubular acidosis
    • Hypomagnesaemia
    • Systemic alkalosis
  • Intestinal loss
    • Intestinal fluid loss (vomiting/diarrhoea)
  • Increased cellular uptake
    • Salbutamol
    • Insulin
    • Systemic alkalosis
Management
  • >2.5mmol/L: potassium supplements (e.g. Sando-K 2 tablets BD/TDS – review dose daily based on K+ level), or 20-40mmol potassium chloride in each litre IV fluids
  • <2.5mmol/L: 40mmol/L potassium chloride in 1L 0.9% saline/5% dextrose over 4-6 hours (NEVER give >10mmol/hour K+ outside ICU)
  • Recheck potassium level as appropriate
  • Treat cause 

Hyperkalaemia 

→ arrhythmias, lethargy, muscle weakness 

Causes
  • Reduced renal excretion
    • Acute/chronic kidney injury
    • Drugs (potassium-sparing diuretics, ACE inhibitors, NSAIDs)
    • Aldosterone deficiency (Addison’s disease/adrenal insufficiency) – ↓Na+ ↑K+
    • Systemic acidosis
  • Excess K+ load
    • Iatrogenic
    • Massive blood transfusion
  • Release from intracellular fluid
    • Systemic acidosis
    • Tissue breakdown, e.g. rhabdomyolysis, haemolysis, tumour lysis syndrome, burns, crush injury

NB: may be due to pseudohyperkalaemia (haemolysis/EDTA-contaminated sample).

Management
  • Acute management
  • ECG and 3-lead cardiac monitoring
    • Changes: flat wide P waves, wide bizarre QRS, tall tented T waves
  • Calcium gluconate 30ml 10% IV over 15 minutes
    • Protects myocytes (required if there are ECG changes; also consider if severe, i.e. ≥6.5mmol/L, without ECG changes)
    • Works in minutes – check ECG changes resolved; repeat dose if no effect within 10 minutes
    • Lasts 30-60 minutes
  • Actrapid insulin 10 units in 125ml 20% dextrose IV over 30 minutes + 10mg salbutamol neb
    • Temporarily shifts potassium into cells
    • There is a risk of hypoglycaemia: monitor capillary glucose before, during and regularly after for 12 hours. Give 10% glucose infusion at 50ml/h for 5 hours after, if the pre-treatment capillary glucose is <7mmol/L.
    • Gradually decreases potassium and lasts 1-2 hours, after which there is usually a slow rebound
    • Check K+ has normalised after 2 hours (dose can be repeated if not) and check again a few hours later
    • Nebulised salbutamol may be used in addition for similar but lesser effect – lasts 2 hours
  • Sodium zirconium cyclosilicate 10g PO TDS for up to 72 hours
    • Works slowly 
    • Only treatment that actually removes potassium from body
    • May start with this if only moderate hyperkalaemia, i.e. K+ ≤ 5.9mmol/L
  • Consider renal replacement therapy if above fails (also consider sodium bicarbonate in severe acidosis)
  • Treat cause
  • Recheck potassium level as appropriate

Reference: The Renal Association ‘Treatment of acute hyperkalaemia in adults’ 2020

Calcium

Physiology

  • Arrows indicate movement of calcium under influence of vitamin D and PTH:
  • PTH should increase in response to hypocalcaemia due to hormonal feedback
  • Always look at the corrected calcium value, which is adjusted for albumin

Hypocalcaemia 

→ CATs go numb: Convulsions, Arrhythmias, Tetany, numbness (periorbital, hands, feet)

Causes
  • PTH deficiency (↑PO43-, ↓PTH)
    • Hypoparathyroidism
    • Hypomagnesaemia (magnesium is required for PTH secretion)
    • Cinacalcet
  • Vitamin D deficiency (↓PO43-, ↑PTH)
  • Increased deposition in bones          
    • Bisphosphonates
  • Other causes (↑PO43-, ↑PTH)
    • Chronic kidney disease (inability to hydroxylate 25-OH vitamin D and calcium binding to retained phosphate)
    • Pseudohypoparathyroidism (resistance to PTH)
    • Rhabdomyolysis/tumour lysis syndrome (calcium binds to high phosphate)
Investigation
  • Initial tests
    • Renal function
    • PTH
    • Phosphate, magnesium
Management
  • Severe (<1.9mmol/L or symptomatic): calcium gluconate 10-20ml 10% in 50-100ml 5% dextrose IV over 10 minutes with cardiac monitoring – may be repeated until asymptomatic and can be followed by an infusion if required based on calcium level (50ml 10% calcium gluconate in 500ml 0.9% saline or 5% dextrose at 50-100ml/hour)
  • Mild (>1.9mmol/L and asymptomatic): calcium supplements (e.g. Sandocal 1000 2 tablets BD) – review dose daily based on calcium level
  • Treat cause: in severe vitamin D deficiency, load with 50,000 units colecalciferol once weekly for 6 weeks; in mild vitamin D deficiency, give 800 units once daily long-term; or, if calcium and vitamin D deficient, give Adcal-D3 long-term; in end-stage CKD-associated vitamin D deficiency, use alfacalcidol (1-α hydroxycholecalciferol) instead because the kidney disease impairs the terminal hydroxylation required for vitamin D synthesis.

Reference: Society for Endocrinology ‘Emergency management of acute hypocalcaemia in adult patients’ 2016

Hypercalcaemia 

→ ‘painful bones, renal stones, abdominal groans, and psychic moans’

Causes
  • PTH excess
    • Primary hyperparathyroidism (↑PTH) or tertiary hyperparathyroidism (↑↑↑PTH)
    • Ectopic PTH/PTH-related peptide secretion (e.g. squamous cell lung cancer)
  • Vitamin D excess
    • Excessive vitamin D intake
    • Granulomatous diseases (e.g. sarcoidosis)
  • Increased release from bones
    • Bony metastasis (↑ALP)
    • Myeloma (normal ALP)
    • Thyrotoxicosis (mechanism unknown)
  • Other causes 
    • Drugs that decrease renal excretion (e.g. thiazide diuretics)

NB: dehydration is also a common cause. (Urea and albumin also likely raised.)

Investigation

Investigate for cause if not clear:

  • Initial tests: renal function, ALP, PTH, phosphate, vitamin D
  • Myeloma screen
  • CT chest, abdomen and pelvis and/or isotope bone scan (if malignancy/bony metastasis suspected)
Management
  • IV fluids: replace fluid deficit and keep patient well hydrated (e.g. . 0.9% saline 4-6L in 24 hours)
  • IV bisphosphonate (e.g. zoledronic acid 4mg IV): may be used in severe hypercalcaemia (>3.5mmol/L or symptomatic) if calcium stops falling with IV fluids alone. One-off dose; generally takes a few days to work. Dose may be reduced for poor renal function. 
  • Treat cause
  • Recheck calcium level as appropriate

Reference: Society for Endocrinology ‘Emergency management of acute hypercalcaemia in adult patients’ 2016

Magnesium 

Hypomagnesaemia 

→ lethargy, muscle weakness/cramps, tremors, arrhythmias, seizures

Causes
  • Reduced intake
    • Poor nutritional intake 
    • Malabsorption
    • Alcoholism 
  • Excess loss
    • GI loss, e.g. severe diarrhoea, vomiting, NG losses, proton pump inhibitors
    • Renal loss, e.g. ketoacidosis, renal tubular diseases, hyperaldosteronism, diuretics, aminoglycosides

NB: hypomagnesaemia can cause hypokalaemia (magnesium normally inhibits renal potassium excretion) and hypocalcaemia (magnesium is required for PTH secretion and sensitivity)  

Management
  • PO: magnesium aspartate 1 sachet (10mmol) OD/BD – review dose daily based on magnesium level
  • IV: no clinical guidelines. Use local hospital protocol, example practice: 5grams (20mmol) magnesium in 500ml 0.9% saline over 5 hours
  • Correct hypomagnesaemia before concurrent hypokalaemia and hypocalcaemia if possible 
  • Recheck magnesium level as appropriate

Phosphate 

Hypophosphataemia 

→ lethargy, muscle weakness (skeletal, cardiac and diaphragmatic), change in mental state

Causes
  • Reduced intake/absorption
    • Vitamin D deficiency
    • Poor nutrition
    • Malabsorption (including due to alcoholism and drugs, e.g. antacids) 
  • Increased use (phosphate shifts into cells to produce ATP from ADP for energy stores)
    • Refeeding syndrome
    • Insulin therapy
    • Alkalosis
  • Excess renal loss
    • Primary hyperparathyroidism
    • Renal tubular diseases 
Management
  • PO: Phosphate-Sandoz 1-2 tablets TDS – review dose daily based on phosphate level
  • IV: no guidelines or licenced preparations and practice varies. Use local guidelines. Examples: Phosphate Polyfusor (50mmol in 500ml), 100-300ml over 12-24 hours depending on severity and patient weight or sodium glycerophosphate 10mmol in 500ml 0.9% saline over 12 hours – must give through different cannula to other electrolytes if co-administering
  • Do not give if hypercalcaemic or oliguric
  • Recheck phosphate level as appropriate

Try some scenarios

Find the normal lab values here.

A patient presents with worsening right heart failure with extensive peripheral oedema. She normally takes bumetanide 1mg BD, eplerenone 25mg OD and ramipril 2.5mg OD. Blood tests are taken: Na+ 120, K+ 4, Ur 14, Cr 288. Her kidney function and sodium were normal when last checked 6 months ago.

What abnormalities have you identified on the blood test and what is the likely reason for them?

Oops! This section is restricted to members. Click here to signup!

How would you manage the patient?

Oops! This section is restricted to members. Click here to signup!

You are on an acute medical unit shift. You are reviewing a patient referred in by their GP. The patient is a 42 year old with a history of recurrent UTIs, for which she takes prophylactic nitrofurantoin. She had a blood test because she was feeling tired. She was referred in due to the results, which showed: Na+ 144, K+ 6.9, Ur 25, Cr 780. The patient is systemically well and observations are normal. She appears euvolaemic.

Which initial investigations would you consider?

Oops! This section is restricted to members. Click here to signup!

What are your priorities in management? Include doses if you would give any medications.

Oops! This section is restricted to members. Click here to signup!

What are the indications for acute renal replacement therapy and does this patient require it?

Oops! This section is restricted to members. Click here to signup!

The patient has a normal urine dipstick and a normal ultrasound KUB. Her FBC shows a mild eosinophillia. What is the most likely diagnosis?

Oops! This section is restricted to members. Click here to signup!

A patient with known prostate cancer with bony metastasis presents with confusion. A calcium level (corrected) is elevated at 3.6mmol/L.

How would you treat the hypercalcaemia?

Oops! This section is restricted to members. Click here to signup!

Which ECG changes may be observed?

Oops! This section is restricted to members. Click here to signup!

Try some interpretation stations

  1. Hyperkalaemia
  2. Diabetic ketoacidosis
  3. Find lots more interpretation stations here

2 Comments

  1. Sylvia says:

    Nice notes☝️

    1. Samuel says:

      Thanks Sylvia for your valuable comment, glad you’re enjoying the site!

Leave a Reply